Browsing by Subject "Glucocorticoidrezeptor"

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Diurnal and photoperiodic effects on the immune system and glucocorticoid signaling in domestic pigs
(2019) Engert, Larissa; Stefanski, Volker
Physiology and behavior of humans and animals display pronounced diurnal and seasonal rhythmic variations. Diurnal rhythms are controlled by daylight and seasonal rhythms are adjusted by the photoperiod, i.e., the relative span of light per day. Modern human life and housing conditions of livestock are often directed against natural daylight conditions and thus, may entail circadian disruption causing misalignment between the central circadian pacemaker and peripheral tissues. Thereby, glucocorticoids are regarded as a main link between these compartments. Circadian disruption might be detrimental for health, in particular affecting immune function, which was mainly investigated in humans and nocturnal rodents but underlying mechanisms are not clearly defined yet. Therefore, the main objective of the present thesis was to investigate diurnal and photoperiodic effects on the immune system and glucocorticoid signaling as well as potential underlying endocrine, behavioral, and molecular mechanisms of these effects in domestic pigs. Adult male castrated pigs, held under specific lighting schedules, were surgically catheterized to enable blood collection without disturbance of the animals. Initially, domestic pigs were held under standard 12L:12D-lighting conditions and blood samples were taken every 2 hours over periods of up to 50 hours. Cosinor analyses revealed pronounced diurnal rhythmicity in peripheral leukocyte numbers of various immune cell populations. These rhythms were mainly comparable to results in humans and nocturnal rodents in relation to their respective rest-activity cycles, with the exception of porcine neutrophils differing from both species. Moreover, the investigated diurnal rhythms in activity behavior and plasma cortisol concentration confirmed that domestic pigs under the applied experimental conditions are diurnally active like humans. Linear mixed model analyses revealed associations of immune cell counts with plasma cortisol concentration, which also resembles results from humans and rodents. Subsequently, photoperiodic effects on diurnal rhythms in peripheral immune cell numbers were investigated for the first time in any species. Domestic pigs were held either under long day conditions (LD) or under short day conditions (SD) and were sampled every 2 hours over periods of 50 hours. Distinct photoperiodic differences in relative amplitudes and peak times of cell counts in various porcine leukocyte types were found, whereas mesor values did not differ. Moreover, photoperiodic effects on diurnal rhythms in plasma cortisol concentrations and activity behavior were found, which is in agreement with human and primate studies. Generalized linear mixed model analyses again revealed associations of leukocyte counts with plasma cortisol concentration and with activity behavior as well. In summary, the results imply stronger rhythmicity of peripheral immune cell numbers in general under SD than under LD. Common intrinsic mechanisms seem to regulate diurnal rhythms in peripheral leukocyte numbers in most immune cell types in domestic pigs, except for neutrophils again. Finally, to investigate potential molecular differences in diurnal regulation between different immune cell types, glucocorticoid receptor (GR) number and affinity were examined in peripheral blood mononuclear cells (PBMC) and granulocytes of domestic pigs. Thereby, a greater number of GR sites per cell and a higher GR binding affinity in PBMC compared to granulocytes were found, pointing to differences in the molecular mechanisms of glucocorticoid signaling between leukocyte populations. The results of the present thesis project are subsequently discussed in regard to specific implications for immune function and health as well as animal husbandry and welfare. Moreover, a methodological assessment of the approaches used within the thesis project was carried out and finally, suggestions for future research directions were given. In conclusion, the present thesis revealed for the first time diurnal and photoperiodic effects on the immune system as well as glucocorticoid signaling in domestic pigs and uncovered potential underlying mechanisms of these effects. Hence, an additional diurnally active model species in chronoimmunology research was established. Moreover, conducting chronoimmunology research in the porcine species represents an innovative approach in agricultural science and provides entirely new opportunities to improve animal health and welfare. Thereby, future studies might investigate diurnal differences in immune function, clarify the role of different zeitgebers on immune rhythms, and assess potential consequences of stressor exposure at different times of the day.